Lyme disease or Lyme borreliosis is an infectious tick-borne disease, caused by the Borrelia spirochete, a gram-negative microorganism.

Lyme disease is so named because it is generally believed to have first been observed in and around Old Lyme and Lyme, Connecticut in 1975. Before 1975, elements of Borrelia infection were also known as "tick-borne meningopolyneuritis", Garin-Bujadoux syndrome, Bannwarth syndrome or sheep tick fever. It is transmitted to humans by the bite of infected ticks.

History

The disease was first documented as a skin rash in Europe in 1883. Over the years, researchers there identified additional features of the disease, including an unidentified pathogen, its response to penicillin, the role of the Ixodes tick (wood tick) as its vector, and symptoms that included not only the rash but additional ones that affected the nervous system.

Researchers in the US had been aware of tick infections since the early 1900s. For example, an infection called tick relapsing fever was reported in 1905, and the wood tick, which carries an agent that causes Rocky Mountain spotted fever, was identified soon after. However, the full syndrome now known as Lyme disease, was not identified until a cluster of cases thought to be juvenile rheumatoid arthritis occurred in three towns in southeastern Connecticut, in the United States. Two of these towns, Lyme and Old Lyme, gave the disease its popular name.

In 1982 a novel spirochete was isolated and cultured from the midgut of Ixodes ticks, and subsequently from patients with Lyme disease. The infecting agent was first identified by Jorge Benach, and soon after isolated by Willy Burgdorfer, a scientist at the National Institutes of Health who specialized in the study of spirochete microorganisms. The spirochete was named Borrelia burgdorferi in his honor.

Microbiology

The disease is caused by the parasite Borrelia, which has well over three hundred known genomic strains but is usually cultured as Borrelia burgdorferi, Borrelia afzelii and Borellia garinii. Different Borrelia strains are predominant in Europe and North America.

The disease has been found to be transmitted to humans by the bite of infected Ixodes ticks. Not all ticks carry or can transmit this particular disease. It should also be noted that in a few cases the disease may also be transmitted by other blood-sucking parasitic insects such as mosquitoes, fleas or blackflies. However other Borrelia strains (i.e. B. garinii) are probably transmitted this way.

Other tick-borne infections may be transmitted simultaneously with Lyme, including Bartonella, Babesiosis, Ehrlichiosis, and Rickettsia.

Borrelia burgdorferi resembles other spirochetes in that it is a highly specialized, motile, two-membrane, spiral-shaped bacterium which lives primarily as an extracellular pathogen. One of the most striking features of Borrelia burgdorferi as compared with other eubacteria is its unusual genome, which includes a linear chromosome approximately one megabase in size and numerous linear and circular plasmids.

Long-term culture of Borrelia burgdorferi results in a loss of some plasmids and changes in expressed protein profiles. Associated with the loss of plasmids is a loss in the ability of the organism to infect laboratory animals, suggesting that the plasmids encode key genes involved in virulence.

Borrelia burgdorferi may persist in humans and animals for months or years following initial infection, despite a robust humoral immune response. Borrelia burgdorferi is susceptible to antibiotics in vitro. However, there are contradictory reports as to the efficacy of antibiotics in vivo in regard to complete eradication of the bacterium from the host. Borrellia burgdorpherri has been isolated in skin specimens of white-footed mice in museum specimens as far back as the 1870s in Massachusetts.

Transmission

In Europe, Ixodes ricinus, known commonly as the sheep tick, castor bean tick, or European castor bean tick is the transmitter. In North America, "Ixodes scapularis" (a.k.a. black-legged tick or deer tick) has been identified as the key to the disease's spread. This condition had been described in medical literature dating back to the early twentieth century but little to no research had been done until Lyme disease was reintroduced to the medical field in the late 1970s.

The number of cases of the disease have been increasing, as are endemic regions in the United States. Lyme disease is reported in nearly every state in the U.S., but there are concentrated areas in the northeast, mid-Atlantic states, Wisconsin, Minnesota, and northern California. Lyme disease is endemic to Europe and Asia.

Lyme disease has been proven to be congenitally passed from an infected mother to fetus through the placenta during pregnancy. There is some anecdotal, largely unconfirmed evidence of sexual transmission.

It is not necessary for the tick to be attached for 24 hours or longer in order for disease transmission to occur; however, the longer the duration of tick attachment, the greater the risk of disease transmission. Even short-term attachment can result in transmission of the disease. Also, improper tick removal can result in early disease transmission so it is very important to remove a tick properly.

Symptoms

Lyme disease has many symptoms, but skin symptoms, arthritis and various neurological symptoms are usually present. Conventional therapy is with antibiotics.

Acute (early) symptoms

• "bull's-eye" rash (erythema migrans) - a circle or ring of inflamed skin surrounding the initial tick bite) or papular (raised) rash
• fever
• malaise
• fatigue
• headache
• muscle and joint aches in large joints
• sore throat
• sinus infection
• paralysis - usually associated with Lyme meningitis or Rocky Mountain spotted fever.

The incubation period from infection to the onset of symptoms is usually 1–2 weeks, but can be much shorter (a couple of days), or even as long as one month. However, it is possible for an infected person to display no symptoms, or display only one or two symptoms, which can make diagnosis difficult.

Chronic (late) symptoms

• meningitis
• neuropathy - numbness, tingling, burning, itching, oversensitivity
• muscle and joint aches
• tremor, twitches
• Bell's palsy
• pain
• immune suppression
• myalgia
• fatigue
• hallucinations
• short-term memory loss

The late symptoms of Lyme disease can appear months to years from infection. Left untreated, Lyme disease can cause chronic disability, but is rarely fatal. Fatality can occur when the spirochete enters brain fluids and causes meningitis, or due to conductivity defects in the heart. Chronic cases have been known to linger for years before a definitive diagnosis.

Lyme disease is often misdiagnosed as chronic fatigue syndrome, multiple sclerosis, fibromyalgia, rheumatoid arthritis, and many other autoimmune and neurological diseases, which leaves the infection untreated and allows it to further penetrate the organism. If the neurologic form of borreliosis is left untreated for years, it may lead to severe debility of the patient. Spirochetes have been noted in deaths in observed autopsy reports.

Diagnosis

The most reliable method of diagnosing Lyme disease is a clinical exam by an experienced practitioner. Supportive data by laboratory tests is never well-advised due to the known non-validity of the CDC's current testing criteria. In cases where the "bull's eye" rash is present in conjunction with a fever or the patient saw the tick, treatment can begin without any further tests. The "bull's eye" rash only occurs in a small percent of all infections. The rash is not always seen as bullseye and sometimes can be a papule the size of small coin. Sometimes the tick bite can leave no rash at all.

The serological laboratory tests available are the Western blot and ELISA, but neither is a reliable indicator: test results vary between labs and within the same lab, sero-negative results are frequent. It is estimated that about a quarter of all infections don't register on any antibody test, and hence empirical treatment is occasionally warranted if the clinical suspicion remains high despite negative serology.

Polymerase chain reaction (PCR) tests for Lyme disease may also be available to the patient. A PCR test attempts to detect the genetic material (DNA) of the Lyme disease spirochete, where as the Western blot and ELISA tests look for antibodies to the organism. PCR tests are rarely susceptible to false-positive results but can often show false-negative results.

In cases of chronic Lyme disease, diagnosis is often clinical and must take all factors into account (tick bite exposure, symptom history, etc.). Positive diagnosis will continue to be problematic until a more reliable test is developed.

Prognosis

The severity and treatment of Lyme disease can be complicated by simultaneous infection with other tick-borne diseases, also known as coinfections, bacterial load and immune suppression in the patient. The disease is rarely fatal in and of itself. Chronic Lyme disease can cause severe and possibly lifelong disability and morbidity.

Prevention

Avoiding areas in which ticks are found can reduce the probability of contracting Lyme disease. If such places cannot be avoided, exposure to Lyme disease can be reduced by:

• applying insect repellent to exposed skin, especially those containing DEET; Permethrin can also be applied to clothing
• wearing light-coloured clothing so that ticks can be located easily and removed,
• wearing long sleeves and pants and tucking pant bottoms into the tops of socks.

In addition, tick removal immediately when found may prevent infection. It is an excellent idea to preserve the tick and have it tested for Lyme disease if the bite occurred in an endemic area. Carefully remove the tick with a pair of tweezers. Take extra care to preserve as much of the tick as you can for identification and laboratory testing.

A vaccine against the North American strain of the virus was available between 1998 and 2002. When taking it off the market, the manufacturer cited poor sales, though some people believe that the actual reason was that the vaccine was not safe or effective at all. [1].

Treatment

Traditional treatment of acute Lyme disease usually consists of a minimum two-week to one-month course of antibiotics, preferably doxycycline (two 200 mg capsules a day).

With the chronic late-stage form of the disease, it may be necessary to continue antibiotic treatment for months or even years. In some cases, immunomodulating drugs are necessary. Not all chronic or tertiary cases are resolved.

The most effective antibiotic treatment in the chronic stage appears to be ceftriaxone (Rocephin®), given intravenously (as oral antibiotics are often ineffective at completely eradicating the disease in any but the initial/early stage). This may, however, cause problems for sensitive patients, as ceftriaxone can cause gallbladder problems. Since there are a maze of different borrelia strains - which can not be identified in vivo - it is often the treating physician's educated guess as to which antibiotic will best treat the given strain a patient has.

External links

• Lyme Disease Association
• Time for Lyme
• The Lyme Disease Foundation
• International Lyme and Associated Diseases Society
• Lyme Disease Medical Literature Summaries
• Lyme Disease Network
• Lyme Disease Articles and Information
• Lyme Disease Actioncs:LymeskГЎ boreliГіza

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